Dr. Wu trades practice for doing stem-cell research

Dr. Wu trades practice for doing stem-cell research

Dr. Ping Wu threw herself into stem-cell research so she could save lives.

It didn't occur to her she would be slowed by a rancorous national debate that has pitted scientists and patients against politicians and religious leaders.

These are hot times for stem-cell researchers and Americans divided about their work. Stem-cell research, pro and con, came up repeatedly during the presidential campaign. The recent death of actor Christopher Reeve, a tireless advocate, fueled the fire. On Election Day, Americans chose a president advocating tight control, but California voters kept the issue burning by approving a $3 billion, state-run research effort.

Wu says she's focused on patients, not politics. "Christopher Reeve was an inspiration to me," says the associate professor of neuroscience and cell biology at the University of Texas Medical Branch. "I am more motivated than ever to harness the potential of stem cells into a therapeutic approach."

Stem cells, or master cells, are the microscopic specks that can morph into any one of more than 200 cell types in the body. The hope is they will be able to replace damaged cells and help with a wide range of devastating diseases and injuries.

In 2001 Wu discovered a reliable method for transforming stem cells into neural, or nerve, cells in rats. More recently, she proved at least some of those replacement nerve cells canreach the targeted muscles.

"Those are potentially huge advancements for patients with Alzheimer's disease, Lou Gehrig's disease and Parkinson's," says Dr. Claire Hulsebosch, professor of neuroscience and cell biology at UTMB. "The dogma used to be that injured nerve cells died and couldn't be replaced. Her research has just busted that."

The stem-cell debate has caused dissension even among scientists, Clifton says. He reminds that the research is grossly underfunded, and there are many questions to answer before clinical trials can be considered.

More controversy

Of the three types of stem cells, most of the controversy focuses on embryonic cells — harvested from fertilized eggs — and fetal cells — harvested from aborted or miscarried fetuses. While they seem to be most promising in the war against disease, many Americans object to their use.

Clifton explains they compare the use of the embryonic cells to abortion, consider the use of the aborted or miscarried fetuses unethical, and they're also concerned scientists will create the embryos and fetuses for the sole purpose of stem-cell research.

Striving to moderate the debate, Clifton says the use of adult stem cells — the injured patient's own tissue — might be a solution. "But those cells don't duplicate as rapidly, and they are less willing to become anything we want them to be. That's the huge advantage of the embryonic and fetal stem cells."

Wu says an untapped and perhaps noncontroversial source of embryonic stem cells might be the unused and unwanted embryos at fertility banks. "Why store them forever or discard them when they could be used to treat devastating diseases?"

Wu, born in Beijing, China, 43 years ago, thought she wanted to be a doctor when she was a child. She hadn't finished her medical training, however, when she realized she needed a career change.

The problem was watching patients die because their diseases had no cures.

That decision brought the unassuming Wu from China to the United States, from an M.D. to a Ph.D, from patients and conventional therapies to rats and human stem cells.

Endless possibilities

The seemingly limitless possibilities first attracted Wu to the field in 1996, when she was an instructor at
Harvard University
.

In 1999, the expert in degenerative brain diseases and spinal cord injuries joined the faculty at UTMB, hoping to tackle stem-cell research herself. The problem was a small lab, limited funds and no stem cells. Right before Christmas she wrote to Dr. Clive Svendsen, then at the University of Cambridge, now at the University of Wisconsin.

Wu knew quite a bit about genetic engineering, and she was glad to share her information. Perhaps he could send her some stem cells?

"This was Dec. 23," Wu says. "I didn't expect a response, at least not until after the holidays."

Svendsen responded the next day, and in January 2000 Wu received a small vial that contained about a million fetal stem cells from discarded brain tissue. Under her careful supervision, they grew and multiplied.

A breakthrough

In 2000 and 2001, Wu received $75,000 from the
John Sealy Memorial Endowment Fund
and $300,000 in seed money from TIRR/Mission Connect. That money helped launch her first stem-cell project. She knew the stem cells could differentiate into many types of other cells. She also knew that she needed nerve cells to replace those damaged or destroyed by neurological disorders and spinal cord injuries.

How to train the stem cells to become nerve cells? She injected the human stem cells into rat brains and rat spinal cords.

The stem cells did not become nerve cells.

Back at the drawing board, she treated the stem cells with a cocktail of chemicals. When she got the recipe just right, almost 90 percent of the grafted cells became nerve cells.

That breakthrough was published in the journal Nature Neuroscience in 2002.

"I remember so many phone calls and e-mails," Wu says. "Patients contacted me from all over the world."

She had to tell them that clinical trials are many years away. Still, she plugged away.

Damaged cells

When Wu grafted treated stem cells into the damaged spinal cords of rats, she found they showed slight but significant improvements. She also found the primed stem cells made an even larger impact on rats with motor-nerve degeneration. "Our cells replaced the damaged cells and made a connection, by growing wirelike cables, that reached the targeted muscles."

It seems to be another breakthrough for Wu, who says these latest results will be published in the next few months in the scientific journal Neuroscience. "I'm not talking about a huge improvement, but some improvement," she says. "It shows we're on the right track."

Once more Wu is back in the lab, mixing chemicals and hoping to improve on the function of the stem cells turned nerve cells.

Spinal-cord injuries are complicated to treat, Wu says, because of nerve loss, inflammation, toxins at the injury site and scarring. Another Mission Connect scientist, Dr. Stephen Davies, is working with a naturally occurring substance produced in the body to eliminate scar formations.

Wu says she hopes they'll collaborate soon on the spinal cord issues.

"For patients to recover significantly, it will take a combined approach that includes stem cells, scar and anti-inflammation strategies and, later, physical therapy."

Wu spends more hours than she cares to count on work. Some of that time is spent collaborating with her husband, Yongjia Yu, also a UTMB scientist. Together, they devote their free time to their son, Frankie, who is 11 and interested in karate, Boy Scouts and drumming. At one time he considered becoming a scientist like his parents. Then the thought passed.

Wu says her son is still young. He has plenty of time to pick a career.

In the meantime, mother and son lock horns over chess and Chinese checkers.